Momelotinib noninferior to ruxolitinib for spleen response in myelofibrosis

June 13, 2017

CHICAGO — Spleen response with momelotinib appeared noninferior to that of ruxolitinib among treatment-naive patients with myelofibrosis, according to results from the phase 3 Simplify clinical trial presented at ASCO annual meeting.

Momelotinib (Gilead Sciences) did not meet noninferiority criteria for the key secondary endpoints of symptom response, but demonstrated an association with a reduced transfusion requirement.

“Momelotinib has been demonstrated with this anemia benefit to potentially have ... mechanisms of action to impact anemia,” Ruben A. Mesa, MD, deputy director of Mayo Clinic Cancer Center in Arizona and HemOnc Today Editorial Board member, said during his presentation. “In the setting of momelotinib, it could potentially have an impact on the pathway because it inhibits type 1 activin A receptor; receptor leads to increased hepcidin gene expression; hepcidin decreases plasma iron; and hepcidin is elevated in myelofibrosis. This is a specific mechanism of action that has been validated in a rodent model.”

Patients demonstrated a transfusion dependence rate of 30.2% with momelotinib compared with 40.1% with ruxolitinib, indicating momelotinib failed to meet noninferiority criteria for the key secondary endpoints of symptom response.

The most common grade 3 or worse adverse events among patients treated with momelotinib included thrombocytopenia (7%) and anemia (6%). Among patients treated with ruxolitinib, the most common events included anemia (23%), thrombocytopenia (5%) and neutropenia (5%).

Seven percent of patients in the momelotinib group had grade 3 or worse infections compared with 3% of patients in the ruxolitinib group.

Disclosures: Mesa reports honoraria from AOP Orphan Pharmaceuticals, Novartis and Shire; consultant/advisory roles with Baxalta, Galena Biopharma, Incyte and Novartis; research funding to his institution from Celgene, CTI, Genentech, Gilead Sciences, Incyte, NS Pharma, Pfizer, Pharmaessentia and Promedior; and travel, accommodations and expenses from AOP Orphan Pharmaceuticals, Incyte and Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

CHICAGO — Spleen response with momelotinib appeared noninferior to that of ruxolitinib among treatment-naive patients with myelofibrosis, according to results from the phase 3 Simplify clinical trial presented at ASCO annual meeting.

Momelotinib (Gilead Sciences) did not meet noninferiority criteria for the key secondary endpoints of symptom response, but demonstrated an association with a reduced transfusion requirement.

“Momelotinib has been demonstrated with this anemia benefit to potentially have ... mechanisms of action to impact anemia,” Ruben A. Mesa, MD, deputy director of Mayo Clinic Cancer Center in Arizona and HemOnc Today Editorial Board member, said during his presentation. “In the setting of momelotinib, it could potentially have an impact on the pathway because it inhibits type 1 activin A receptor; receptor leads to increased hepcidin gene expression; hepcidin decreases plasma iron; and hepcidin is elevated in myelofibrosis. This is a specific mechanism of action that has been validated in a rodent model.”

Patients demonstrated a transfusion dependence rate of 30.2% with momelotinib compared with 40.1% with ruxolitinib, indicating momelotinib failed to meet noninferiority criteria for the key secondary endpoints of symptom response.

The most common grade 3 or worse adverse events among patients treated with momelotinib included thrombocytopenia (7%) and anemia (6%). Among patients treated with ruxolitinib, the most common events included anemia (23%), thrombocytopenia (5%) and neutropenia (5%).

Seven percent of patients in the momelotinib group had grade 3 or worse infections compared with 3% of patients in the ruxolitinib group.